The fibrous elastic fiber, a primary site of lipid deposition and calcification in the vascular wall, derives from intermolecular cross-linking of lysyl residue side chains..sup.1,2 The precursor protein of the core of the elastic fiber, tropoelastin,.sup.3-6 has been shown to contain repeating peptide sequences.sup.7,8 -- a tetrapeptide (Val.sub.1 -Pro.sub.2 -Gly.sub.3 -Gly.sub.4), a pentapeptide (Val.sub.1 -Pro.sub.2 -Gly.sub.3 -Val.sub.4 -Gly.sub.5), and a hexapeptide (Ala.sub.1 -Pro.sub.2 -Gly.sub.3 -Val.sub.4 -Gly.sub.5 -Val.sub.6) it being understood that Val represents the residue of valine, Pro the residue of proline, Gly the residue of glycine, Ala the residue of alanine and the subscripts the position in the peptide molecule, all of the amino acid residues, with the exception of that of glycine, being in the L-configuration. These sequences, their oligomers and high polymers have been synthesized and their conformations characterized..sup.9-14
The molecular system of interest has been examined in three different states -- solution, coacervate and fibrous. The coacervate is the key to bridging from the solution to the fibrous state. Coacervation, a reversible, concentration-dependent phase separation elicited in this case by temperature, is an uncommon property exhibited by tropoelastin, by .alpha.-elastin (a chemical fragmentation product of fibrous elastin), by the polypentapeptide and by the polyhexapeptide. All of these molecular systems are soluble in water at low temperatures, but, on raising the temperature, the solutions become cloudy and the light scattering elements coalesce to form a more dense phase which is about 60% water by volume. The coacervate is the stable state at body temperature; the coacervate contains the same volume percent water (.about.60%) as fibrous elastin, and the coacervate is filamentous with periodicities similar to those of fibrous elastin. For these reasons, the coacervate is taken to be a model of the relaxed fibrous state and the process of coacervation is viewed as a key step in elastogenesis which concentrates and aligns the sub-unit prior to covalent crosslinking.
All of the prior research, however, has failed to result in the obtaining of a product sufficiently insoluble to have practical utility in physiological applications.
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